Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease - PubMed (original) (raw)

. 1996 Oct 1;184(4):1425-33.

doi: 10.1084/jem.184.4.1425.

M S Lucia, K C Flanders, L Chesler, Q W Xie, T W Smith, J Weidner, R Mumford, R Webber, C Nathan, A B Roberts, C F Lippa, M B Sporn

Affiliations

• PMID: 8879214
• PMCID: PMC2192831
• DOI: 10.1084/jem.184.4.1425

Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease

Y Vodovotz et al. J Exp Med. 1996.

Abstract

In Alzheimer's disease (AD), affected neurons accumulate beta amyloid protein, components of which can induce mouse microglia to express the high-output isoform of nitric oxide synthase (NOS2) in vitro. Products of NOS2 can be neurotoxic. In mice, NOS2 is normally suppressed by transforming growth factor beta 1 (TGF-beta 1). Expression of TGF-beta 1 is decreased in brains from AD patients, a situation that might be permissive for accumulation of NOS2. Accordingly, we investigated the expression of NOS2 in patients with AD, using three monospecific antibodies: a previously described polyclonal and two new monoclonal antibodies. Neurofibrillary tangle-bearing neurons and neuropil threads contained NOS2 in brains from each of 11 AD patients ranging in age from 47 to 81 years. NOS2 was undetectable in brains from 6 control subjects aged 23-72 years, but was expressed in small amounts in 3 control subjects aged 77-87 years. Thus, human neurons can express NOS2 in vivo. The high-output pathway of NO production may contribute to pathogenesis in AD.

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References

1. 1. Neurology. 1984 Jul;34(7):939-44 - PubMed
2. 1. J Exp Med. 1996 May 1;183(5):2337-42 - PubMed
3. 1. J Immunol. 1990 Aug 1;145(3):940-4 - PubMed
4. 1. Neurology. 1991 Apr;41(4):479-86 - PubMed
5. 1. FEBS Lett. 1992 Aug 3;307(3):287-93 - PubMed

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